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Crucial role of methyla0on inMembrane uidity
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Chewing the Fat about Cholesterol Amanda Yarnell, C&EN, May 3, 2004
Molecule plays a key role in controlling theorganiza8on and elas8city of cell membranes
Subtle changes in the cholesterol molecule canhave drama8c effects on membrane elas8city.
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Two sides to the cholesterol story;everything in modera0on
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Two sides to thecholesterol story;everything inmodera0on
In the mature brainthe highest
cholesterol contentis found in myelin
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A new look at lipids in nervesNature Reviews, Microarrays Collec8on, March 2004, p. 5
muta8ons in Lpin1 lead to peripheral
neuropathy, and to the dysregula8on of genesthat par8cipate in lipid metabolism in nerves.
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Lipids Play a Role in Myelin Stability Ra8o of sphingomyelin to cholesterol Role of methyla8on in membrane uidity Regulatory role of FAS Membrane uidity in other types of neurological inamma8on LDL is the receptor for reelin Transloca8on of PS Sta8n use for MS, Alzheimers
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Rela8onship to phospholipid methyla8on and membrane uidity described by Deth
Brain phospholipids decreased with increased levels of insulin
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Role of the D4 dopamine receptor
in membrane uidity
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In general, receptor ac8va8on occurs by phosphoryla8on via PKC at threoninehot spots
EXCEPTION is the D4 receptor where it ismethionineac8va8on by MAT at the hot spot.
This suggests that D4 would be par8cularly sensi8ve to issues with MAT.Ac8va8on requires dona8on of a methyl group by the D4 receptor through MAT.IMPLIES More direct effects due to methyla8on pathway than for otherdopamine receptors.
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The main effect of adding one or more methyl groups to PE is that the phospholipid moleculescannot pack as close to one another as before
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Dopamine and 5 methyl THF regulate the D4 receptor.
Rela8onship to COMT ++ status
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Excerpt from Deth et al
mercury
thimerosal
aluminum
Thimerosal, lead, mercury, aluminum depress PLM
